The objectives are to study the effects of certain environmental pollutants and hepatotoxins with the retrograde intrabiliary injection (R11) technique and gain some insight into how these agents produce effects on the liver. Some studies have already been initiated using CC14 as a model compound to produce liver damage. We have found that CC14 liver damage produces a "dicrotic notch" in the recollection curve for the retrogradely injected compounds. Several approaches are proposed to investigate this finding based on the proposition that this effect of CC14 is on duct and ductular sites in the biliary tree. Ability to detect functional damage at such sites is a new finding for CC14. For obvious reasons, we will broaden the study to include other hepatotoxins and environmental pollutants. CO in initial trials, by virtue of its effect to depress bile flow, produces changes in the shape of the recollection curves for the compounds given by retrograde intrabiliary injection. Attempts will be made to differentiate effects of hypoxia from those of CO. Because dichloromethane type compounds are converted by metabolism to CO, possible intrahepatic release of CO and effects of this release will be evaluated. A study of selected compounds which produce liver damage will be made. Allylisopropylacetamide will be studied for hepatic porphyric effects. Beryllium which produces midzonal hepatic necrosis will be compared to CC14; ethionine will be studied as a model compound to produce proliferation of the bile ducts and decrease of ATP levels. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on hepatic excretory function will be assessed and studies on the biliary excretion of environmental pollutants such as the polychlorinated biphenyls will be initiated. BIBLIOGRAPHIC REFERENCES: Peterson, R.E., Seymour, J.L. and Allen, J.R.: Distribution and Biliary Excretion of Polycholorinated Biphenyls in Rats, Toxicol. Appl. Pharmacol. 38, 609, 1976.